HCN4 subunit expression in fast-spiking interneurons of the rat spinal cord and hippocampus

Hughes, D.I., Boyle, K., Kinnon, C.M., Bilsland, C., Quayle, J., Callister, R.J. and Graham, B.A. (2013) HCN4 subunit expression in fast-spiking interneurons of the rat spinal cord and hippocampus. Neuroscience, 237, pp. 7-18. (doi:10.1016/j.neuroscience.2013.01.028)

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Abstract

Hyperpolarisation-activated (Ih) currents are considered important for dendritic integration, synaptic transmission, setting membrane potential and rhythmic action potential (AP) discharge in neurons of the central nervous system. Hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels underlie these currents and are composed of homo- and hetero-tetramers of HCN channel subunits (HCN1–4), which confer distinct biophysical properties on the channel. Despite understanding the structure–function relationships of HCN channels with different subunit stoichiometry, our knowledge of their expression in defined neuronal populations remains limited. Recently, we have shownthat HCN subunit expression is a feature of a specific population of dorsal horn interneurons that exhibit high-frequency AP discharge. Here we expand on this observation and use neuroanatomical markers to first identify well-characterised neuronal populations in the lumbar spinal cord and hippocampus and subsequently determine whether HCN4 expression correlates with high-frequency AP discharge in these populations. In the spinal cord, HCN4 is expressed in several putative inhibitory interneuron populations including parvalbumin (PV)-expressing islet cells (84.1%; SD: ±2.87), in addition to all putative Renshaw cells and Ia inhibitory interneurons. Similarly, virtually all PVexpressing cells in the hippocampal CA1 subfield (93.5%;±3.40) and the dentate gyrus (90.9%; ±6.38) also express HCN4. This HCN4 expression profile in inhibitory interneurons mirrors both the prevalence of Ih sub-threshold currents and high-frequency AP discharge. Our findings indicate that HCN4 subunits are expressed in several populations of spinal and hippocampal interneurons, which are known to express both Ih sub-threshold currents and exhibit high-frequency AP discharge. As HCN channel function plays a critical role in pain perception, learning and memory,and sleep as well as the pathogenesis of several neurologicaldiseases, these findings provide important insights into the identity and neurochemical status of cells that could underlie such conditions.

Item Type:Articles
Keywords:HCN channels, spinal cord, hippocampus
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Boyle, Dr Kieran and Hughes, Dr David I
Authors: Hughes, D.I., Boyle, K., Kinnon, C.M., Bilsland, C., Quayle, J., Callister, R.J., and Graham, B.A.
Subjects:Q Science > QP Physiology
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Neuroscience
Publisher:Elsevier
ISSN:0306-4522
ISSN (Online):1873-7544
Published Online:25 January 2013

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
571071Modulating cutaneous afferent input: Identifying a source of presynaptic (axo-axonic) inputs in the mouse spinal dorsal hornDavid I HughesBiotechnology and Biological Sciences Research Council (BBSRC)BB/J000620/1RI NEUROSCIENCE & PSYCHOLOGY